Pharmacokinetic disposition of theophylline in horses after intravenous administration.

The research investigated how the drug theophylline, given intravenously to horses, is processed within their bodies with regards to dosage and time, particularly focused on those horses with chronic obstructive pulmonary disease.

Objective & Methodology

• Researchers aimed to understand the pharmacokinetics, which is how the body absorbs, distributes, metabolizes, and excretes a drug, of theophylline in horses.
• Initially, the study involved six healthy horses that were given a single intravenous dose of aminophylline, which converts to theophylline in the body.
• The serum concentration of theophylline in these horses was then measured at multiple intervals upto 15 hours after the drug administration.

Findings

• The theophylline levels in five out of the six horses were best reflected by a 2-compartment open model which categorises the body into two parts: a central compartment (blood plasma and highly perfused organs) and a peripheral compartment (less perfused tissues).
• However, in one horse, the data fit best with a 1-compartment open model, suggesting variability among individual animals and their responses.
• Based on this, the researchers calculated a variety of pharmacokinetic parameters including elimination half-life, distribution half-life, apparent specific volume of distribution, apparent specific volume of central compartment, and clearance.

Experiment with COPD Horses

• In the second part of the study, three horses with reversible chronic obstructive pulmonary disease (COPD) were given varying doses of aminophylline, in a single IV administration, under distressing conditions.
• These horses were observed to exhibit a reduction in the severity of COPD symptoms following the administration of aminophylline at doses of 9, 12, or 15 mg/kg of body weight.
• Measurements taken half an hour post administration showed a significant drop in the horses’ partial pressure of carbon dioxide and a significant increase in blood pH (more alkaline).

Conclusion

• The research demonstrates a relationship between theophylline dose and its distribution and effect on horses, particularly those suffering from COPD.
• This can guide future treatments of horses with respiratory distress conditions using theophylline. However, individual variability must be considered when designing dosing schedules.